Many industrial chemicals and pesticides contain a chloro-olefin group, or are metabolized via chloro-olefins. Recently, several chloro-olefins, e.g. vinylchloride, have been shown to be mutagenic and/or carcinogenic, and metabolic epoxidation has been implicated as mediating this biological activity. DDT is metabolized to the chloro-olefin DDE in the mouse, and both DDT and DDE are liver carcinogens in this species. We propose to examine the hypothesis that DDE is metabolically activated by epoxidation in the mouse by examining various chemical and biological activities of a series of four model chloro-olefins with structures intermediate between vinylchloride and DDE. We propose to synthesize chloroepoxides of the 4 model compounds, as well as the epoxides of DDE and its reported metabolite DDMU, and determine their thermal stability, and their reactions with model nucleophiles and nucleic acids. The mutagenicity of the chloroepoxides and their rearrangement products, the alpha-chlorocarbonyl compounds and their precursor chloro-olefins will be determined in the Ames' S. typhimurium assay. The in vivo and in vitro metabolism and binding of the chloro-olefins, epoxides and alpha-chlorocarbonyl compounds will be compared in an attempt to relate chemical reactivity in vitro and biological activity. These compounds will also be assayed for carcinogenicity by skin painting in the mouse, as our original hypothesis would predict that the chloroepoxides should be direct-acting carcinogens. Thus it is hoped to determine general principles concerning the importance of metabolic epoxidation in the carcinogenicity of DDT and related organochlorine compounds in the mouse, as an aid to predicting the potential human health hazards of these compounds.